Advanced search
Publication Cover
Expert Opinion on Drug Safety Volume 17, 2018 - Issue 2
Submit an article Journal homepage
513
Views
11
CrossRef citations to date
0
Altmetric
Review

Skin cancer associated with commonly prescribed drugs: tumor necrosis factor alpha inhibitors (TNF-αIs), angiotensin-receptor blockers (ARBs), phosphodiesterase type 5 inhibitors (PDE5Is) and statins -weighing the evidence

Beatrice NardoneDepartment of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USAView further author information
,
Kelsey A. OrrellDepartment of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USAView further author information
,
Paras P. VakhariaDepartment of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USAView further author information
&
Dennis P. WestDepartment of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USACorrespondence[email protected]
View further author information
Pages 139-147 | Received 20 Jul 2017, Accepted 31 Oct 2017, Published online: 08 Nov 2017

  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7–30.
  • Whiteman DC, Green AC, Olsen CM. The growing burden of invasive melanoma: projections of incidence rates and numbers of new cases in six susceptible populations through 2031. J Invest Dermatol. 2016 Jun;136(6):1161–1171.
  • De Vries E, Coebergh JW. Cutaneous malignant melanoma in Europe. Eur J Cancer. 2004 Nov;40(16):2355–2366.
  • American Cancer Society. Cancer facts and figures 2017. 2017 [ cited 2017 May 31]. Available from: https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2017.html
  • Surveillance, Epidemiology, and End Results (SEER) Program. Cancer stat facts: melanoma of the skin. 2017 [cited 2017 May 31]. Available from: https://seer.cancer.gov/statfacts/html/melan.html
  • Nikolaou V, Stratigos AJ. Emerging trends in the epidemiology of melanoma. Br J Dermatol. 2014 Jan;170(1):11–19.
  • Brown T. 100 Best-selling, most prescribed branded drugs through March. 2015 [cited 2017 May 31]. Available from: http://www.medscape.com/viewarticle/844317
  • Liu Y, Fan W, Chen H, et al. Risk of breast cancer and total malignancies in rheumatoid arthritis patients undergoing TNF-α antagonist therapy: a meta-analysis of randomized control trials. Asian Pac J Cancer Prev. 2014;15(8):3403–3410.
  • Jain A, Singh JA. Harms of TNF inhibitors in rheumatic diseases: a focused review of the literature. Immunotherapy. 2013 Mar;5(3):265–299.
  • Buchbinder R, Van Doornum S, Staples M, et al. Malignancy risk in Australian rheumatoid arthritis patients treated with anti-tumour necrosis factor therapy: analysis of the Australian Rheumatology Association Database (ARAD) prospective cohort study. BMC Musculoskelet Disord. 2015 Oct 20;16:309.
  • Mariette X, Matucci-Cerinic M, Pavelka K, et al. Malignancies associated with tumour necrosis factor inhibitors in registries and prospective observational studies: a systematic review and meta-analysis. Ann Rheum Dis. 2011 Nov;70(11):1895–1904.
  • Askling J, Fahrbach K, Nordstrom B, et al. Cancer risk with tumor necrosis factor alpha (TNF) inhibitors: meta-analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data. Pharmacoepidemiol Drug Saf. 2011 Feb;20(2):119–130.
  • Raaschou P, Simard JF, Asker Hagelberg C, et al. Rheumatoid arthritis, anti-tumour necrosis factor treatment, and risk of squamous cell and basal cell skin cancer: cohort study based on nationwide prospectively recorded data from Sweden. BMJ. 2016 Jan 28;352:i262.
  • Raaschou P, Simard JF, Holmqvist M, et al. Rheumatoid arthritis, anti-tumour necrosis factor therapy, and risk of malignant melanoma: nationwide population based prospective cohort study from Sweden. BMJ. 2013 Apr 08;346:f1939.
  • Long MD, Martin CF, Pipkin CA, et al. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology. 2012 Aug;143(2):390–99 e1.
  • Nardone B, Hammel JA, Raisch DW, et al. Melanoma associated with tumour necrosis factor-alpha inhibitors: a Research on Adverse Drug events And Reports (RADAR) project. Br J Dermatol. 2014 May;170(5):1170–1172.
  • McKenna MR, Stobaugh DJ, Deepak P. Melanoma and non-melanoma skin cancer in inflammatory bowel disease patients following tumor necrosis factor-alpha inhibitor monotherapy and in combination with thiopurines: analysis of the Food and Drug Administration Adverse Event Reporting System. J Gastrointestin Liver Dis. 2014 Sep;23(3):267–271.
  • Saliba L, Moulis G, Abou Taam M, et al. Tumor necrosis factor inhibitors added to nonbiological immunosuppressants vs. nonbiological immunosuppressants alone: a different signal of cancer risk according to the condition. A disproportionality analysis in a nationwide pharmacovigilance database. Fundam Clin Pharmacol. 2016 Apr;30(2):162–171.
  • Dreyer L, Mellemkjaer L, Andersen AR, et al. Incidences of overall and site specific cancers in TNFalpha inhibitor treated patients with rheumatoid arthritis and other arthritides - a follow-up study from the DANBIO Registry. Ann Rheum Dis. 2013 Jan;72(1):79–82.
  • Asgari MM, Ray GT, Geier JL, et al. Malignancy rates in a large cohort of patients with systemically treated psoriasis in a managed care population. J Am Acad Dermatol. 2017 Apr;76(4):632–638.
  • Mercer LK, Askling J, Raaschou P, et al. Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics: results from a collaborative project of 11 European biologic registers. Ann Rheum Dis. 2017 Feb;76(2):386–391.
  • Sipahi I, Debanne SM, Rowland DY, et al. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol. 2010 Jul;11(7):627–636.
  • Zhao YT, Li PY, Zhang JQ, et al. Angiotensin II receptor blockers and cancer risk: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2016 May;95(18):e3600.
  • Moscarelli L, Zanazzi M, Mancini G, et al. Keratinocyte cancer prevention with ACE inhibitors, angiotensin receptor blockers or their combination in renal transplant recipients. Clin Nephrol. 2010 Jun;73(6):439–445.
  • Christian JB, Lapane KL, Hume AL, et al. Association of ACE inhibitors and angiotensin receptor blockers with keratinocyte cancer prevention in the randomized VATTC trial. J Natl Cancer Inst. 2008 Sep 03;100(17):1223–1232.
  • De Giorgi V, Gandini S, Grazzini M, et al. Effect of β-blockers and other antihypertensive drugs on the risk of melanoma recurrence and death. Mayo Clin Proc. 2013 Nov;88(11):1196–1203.
  • Koomen ER, Herings RM, Guchelaar HJ, et al. Melanoma incidence and exposure to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Cancer Epidemiol. 2009 Nov;33(5):391–395.
  • Schmidt SA, Schmidt M, Mehnert F, et al. Use of antihypertensive drugs and risk of skin cancer. J Eur Acad Dermatol Venereol. 2015 Aug;29(8):1545–1554.
  • Nardone B, Majewski S, Kim AS, et al. Melanoma and non-melanoma skin cancer associated with angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers and thiazides: a matched cohort study. Drug Saf. 2017 Mar;40(3):249–255.
  • Yoon C, Yang H-S, Jeon I, et al. Use of angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers and cancer risk: a meta-analysis of observational studies. Cmaj. 2011 Oct 4;183(14):E1073–84.
  • Ayta IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int. 1999 Jul;84(1):50–56.
  • Brant WO, Lue TF, Smith JF. Evaluation and management of erectile dysfunction in clinical practice. J Clin Outcomes Manag. 2009;16(2):83–96.
  • Food and Drug Administration. Sildenafil labeling-package insert. [ cited 31 May 2017]. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021845
  • Food and Drug Administration. Tadalafil labeling-package insert. [ cited 11 July 2017]. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021368
  • Li W-Q, Qureshi AA, Robinson KC, et al. Sildenafil use and increased risk of incident melanoma in US men: a prospective cohort study. JAMA Intern Med. 2014 Jun;174(6):964–970.
  • Loeb S, Folkvaljon Y, Lambe M, et al. Use of phosphodiesterase type 5 inhibitors for erectile dysfunction and risk of malignant melanoma. JAMA. 2015 Jun 23-30;313(24):2449–2455.
  • Lian Y, Yin H, Pollak MN, et al. Phosphodiesterase type 5 inhibitors and the risk of melanoma skin cancer. Eur Urol. 2016 Nov;70(5):808–815.
  • Matthews A, Langan SM, Douglas IJ, et al. Phosphodiesterase Type 5 inhibitors and risk of malignant melanoma: matched cohort study using primary care data from the UK Clinical Practice Research Datalink. PLoS Med. 2016 Jun;13(6):e1002037.
  • Pottegard A, Schmidt SA, Olesen AB, et al. Use of sildenafil or other phosphodiesterase inhibitors and risk of melanoma. Br J Cancer. 2016 Sep 27;115(7):895–900.
  • Boor PNB, Polisetty S, Huynh T, et al. Melanoma in men treated with PDE5A inhibitors: a report from the RADAR (Research on Adverse Drug Events And Reports) project. J Am Acad Dermatol. 2016;74(5S1):AB190; P3174.
  • Loeb S, Ventimiglia E, Salonia A, et al. Meta-analysis of the association between phosphodiesterase inhibitors (PDE5Is) and risk of melanoma. J Natl Cancer Inst. 2017 Aug;109(8):djx086.
  • Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. Jama. 2006 Apr 05;295(13):1556–1565.
  • Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996 Oct 03;335(14):1001–1009.
  • Newman TB, Hulley SB. Carcinogenicity of lipid-lowering drugs. Jama. 1996 Jan 03;275(1):55–60.
  • Wong WW, Dimitroulakos J, Minden MD, et al. HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis. Leukemia. 2002 Apr;16(4):508–519.
  • Demierre MF, Higgins PD, Gruber SB, et al. Statins and cancer prevention. Nat Rev Cancer. 2005 Dec;5(12):930–942.
  • Stein EA, Corsini A, Gimpelewicz CR, et al. Fluvastatin treatment is not associated with an increased incidence of cancer. Int J Clin Pract. 2006 Sep;60(9):1028–1034.
  • Kuoppala J, Lamminpää A, Pukkala E. Statins and cancer: a systematic review and meta-analysis. Eur J Cancer. 2008 Oct;44(15):2122–2132.
  • Li X, Wu XB, Chen Q. Statin use is not associated with reduced risk of skin cancer: a meta-analysis. Br J Cancer. 2014 Feb 04;110(3):802–807.
  • Asgari MM, Tang J, Epstein EH Jr., et al. Statin use and risk of basal cell carcinoma. J Am Acad Dermatol. 2009 Jul;61(1):66–72.
  • Dore DD, Lapane KL, Trivedi AN, et al. Association between statin use and risk for keratinocyte carcinoma in the veterans affairs topical tretinoin chemoprevention trial. Ann Intern Med. 2009 Jan 06;150(1):9–18.
  • Wang A, Stefanick ML, Kapphahn K, et al. Relation of statin use with non-melanoma skin cancer: prospective results from the Women’s Health Initiative. Br J Cancer. 2016 Feb 02;114(3):314–320.
  • Food and Drug Administration. FDA drug safety communication: no increase in risk of cancer with certain blood pressure drugs–angiotensin receptor blockers (ARBs). 2011 [cited 2017 May 31]. Available from: https://www.fda.gov/Drugs/DrugSafety/ucm257516.htm
  • Food and Drug Administration. Surveillance: post drug-approval activities. January - March 2016 [ cited 11 July 2017]. Available from: https://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/surveillance/adversedrugeffects/ucm509478.htm
  • Lapeyre-Mestre M, Sapede C, Moore N, et al. Pharmacoepidemiology studies: what levels of evidence and how can they be reached? Therapie. 2013 Jul-Aug;68(4):241–252.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.